βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

Abstract

βII spectrin, the most common isoform of non-erythrocyte spectrin, is a cytoskeleton protein present in all nucleated cells. Interestingly, βII spectrin is essential for the development of various organs such as nerve, epithelium, inner ear, liver and heart. The functions of βII spectrin include not only establishing and maintaining the cell structure but also regulating a variety of cellular functions, such as cell apoptosis, cell adhesion, cell spreading and cell cycle regulation. Notably, βII spectrin dysfunction is associated with embryonic lethality and the DNA damage response. More recently, the detection of altered βII spectrin expression in tumors indicated that βII spectrin might be involved in the development and progression of cancer. Its mutations and disorders could result in developmental disabilities and various diseases. The versatile roles of βII spectrin in disease have been examined in an increasing number of studies; nonetheless, the exact mechanisms of βII spectrin are still poorly understood. Thus, we summarize the structural features and biological roles of βII spectrin and discuss its molecular mechanisms and functions in development, homeostasis, regeneration and differentiation. This review highlight the potential effects of βII spectrin dysfunction in cancer and other diseases, outstanding questions for the future investigation of therapeutic targets. The investigation of the regulatory mechanism of βII spectrin signal inactivation and recovery may bring hope for future therapy of related diseases.

Proteomics and Machine Learning Approaches Reveal a Set of Prognostic Markers for COVID-19 Severity With Drug Repurposing Potential

“…Another ubiquitously present protein βII spectrin was found to be downregulated in severe COVID-19. Given that inadequate βII spectrin might precipitate into arrhythmia, heart failure, or even neurodegeneration (Yang et al, 2021), the findings hold much importance. Two proteins, namely, APOM, known to protect the lungs and kidneys from injuries (Ding et al, 2020), and APOA2, were also downregulated; similar observations were previously reported (Shen et al, 2020).…”

A multipronged deep omics-based investigation of COVID-19 plasma samples identifies key molecular networks of disease severity progression

“…46 Our studies have demonstrated that a crucial factor in platelet biogenesis TPM4 47 is inhibited (FC-1.94, P < 0.001) in severe cases thereby providing novel biological insight into COVID-19 severity. Yet another ubiquitously present protein βII spectrin was found to be downregulated in severe COVID-19, given that inadequate βII spectrin might precipitate into arrhythmia, heart failure, or even neurodegeneration 48 the ndings hold much importance. Two proteins namely APOM which is known to protect the lungs and kidneys from injuries 49 and APOA2 were also downregulated, similar observations were previously reported.…”

COVID-19 plasma deep proteome reveals distinct signatures in severe patients

“…45 Our studies have demonstrated that a crucial factor in platelet biogenesis TPM4 46 is inhibited (FC-1.94, P < 0.001) in severe cases, thereby providing novel biological insight into COVID-19 severity. Another ubiquitously present protein βII spectrin was found to be downregulated in severe COVID-19, given that inadequate βII spectrin might precipitate into arrhythmia, heart failure, or even neurodegeneration 47 the ndings hold much importance. Two proteins, namely APOM, which is known to protect the lungs and kidneys from injuries 48 and APOA2, were also downregulated; similar observations were previously reported.…”